ArticleMolecular psychiatry2011
Calcyon upregulation in adolescence impairs response inhibition and working memory in adulthood.
Article in Molecular psychiatry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- The protein interactome of the Neuron Specific Gene family (NSG1-3).bioRxiv : the preprint server for biology · 2025Article
- Knockout of AMPA receptor binding protein Neuron-specific gene 2 (NSG2) enhances associative learning and cognitive flexibility.Molecular brain · 2024Article
- Knockout of AMPA receptor binding protein Neuron-Specific Gene 2 (NSG2) enhances associative learning and cognitive flexibility.Research square · 2024Article
- Predicting Key Genes and Therapeutic Molecular Modelling to Explain the Association betweenInternational journal of molecular sciences · 2023Article
- Biological Mechanism-based Neurology and Psychiatry: A BACE1/2 and Downstream Pathway Model.Current neuropharmacology · 2023Article
- Global loss of Neuron-specific gene 1 causes alterations in motor coordination, increased anxiety, and diurnal hyperactivity in male mice.Genes, brain, and behavior · 2022Article
- Angiotensin receptor (AT2R) agonist C21 prevents cognitive decline after permanent stroke in aged animals-A randomized double- blind pre-clinical study.Behavioural brain research · 2019Article
- Increased arterial pressure in mice with overexpression of the ADHD candidate gene calcyon in forebrain.PloS one · 2019Article
- Role of angiotensin system modulation on progression of cognitive impairment and brain MRI changes in aged hypertensive animals - A randomized double- blind pre-clinical study.Behavioural brain research · 2018Article
- Dynein binds and stimulates axonal motility of the endosome adaptor and NEEP21 family member, calcyon.The international journal of biochemistry & cell biology · 2017Article
- Hypervulnerability of the adolescent prefrontal cortex to nutritional stress via reelin deficiency.Molecular psychiatry · 2017Article
- Calcyon stimulates neuregulin 1 maturation and signaling.Molecular psychiatry · 2015Article
- A role for synaptic plasticity in the adolescent development of executive function.Translational psychiatry · 2013Review
- Exposure to variable prenatal stress in rats: effects on anxiety-related behaviors, innate and contextual fear, and fear extinction.Behavioural brain research · 2013Article
- Calcyon forms a novel ternary complex with dopamine D1 receptor through PSD-95 protein and plays a role in dopamine receptor internalization.The Journal of biological chemistry · 2012Article
- Chronic adolescent exposure to delta-9-tetrahydrocannabinol in COMT mutant mice: impact on indices of dopaminergic, endocannabinoid and GABAergic pathways.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2012Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Calcyon regulates activity-dependent internalization of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) glutamate receptors and long-term depression of excitatory synapses. Elevated levels of calcyon are consistently observed in brains from schizophrenic patients, and the calcyon gene is associated with attention-deficit hyperactivity disorder. Executive function deficits are common to both disorders, and at least for schizophrenia, the etiology appears to involve both heritable and neurodevelopmental factors. Here, we show with calcyon-overexpressing Cal(OE) transgenic mice that lifelong calcyon upregulation impairs executive functions including response inhibition and working memory, without producing learning and memory deficits in general. As response inhibition and working memory, as well as the underlying neural circuitry, continue to mature into early adulthood, we functionally silenced the transgene during postnatal days 28-49, a period corresponding to adolescence. Remarkably, the response inhibition and working memory deficits including perseverative behavior were absent in adult Cal(OE) mice with the transgene silenced in adolescence. Suppressing the calcyon transgene in adulthood only partially rescued the deficits, suggesting calcyon upregulation in adolescence irreversibly alters development of neural circuits supporting mature response inhibition and working memory. Brain regional immunoblots revealed a prominent downregulation of AMPA GluR1 subunits in hippocampus and GluR2/3 subunits in hippocampus and prefrontal cortex of the Cal(OE) mice. Silencing the transgene in adolescence prevented the decrease in hippocampal GluR1, further implicating altered fronto-hippocampal connectivity in the executive function deficits observed in the Cal(OE) mice. Treatments that mitigate the effects of high levels of calcyon during adolescence could preempt adult deficits in executive functions in individuals at risk for serious mental illness.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.